Mechanistic Insight on Ethanol Driven Swelling and Disruption of Cholesterol Containing Biomimetic Vesicles From Coarse-Grained Molecular Dynamics,Journal of Computational Chemistry

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Mechanistic Insight on Ethanol Driven Swelling and Disruption of Cholesterol Containing Biomimetic Vesicles From Coarse-Grained Molecular Dynamics
Journal of Computational Chemistry ( IF 3.4 ) Pub Date : 2025-03-13 , DOI: 10.1002/jcc.70050
Shobhna ₁ , Ayishwarya Dutta ₁ , Hemant K Kashyap ₁

Affiliation

We have performed coarse-grained (CG) molecular dynamics (MD) simulations to delineate the impact of ethanol (EtOH) on cholesterol (CHOL) containing biomimetic bilayer and vesicle composed of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) lipids. We have first deduced the missing interaction parameters for the POPC-CHOL-EtOH-water system within the SPICA/SDK CG force-field (CG-FF). By monitoring the electron density profiles, the orientational order parameter, and reproducing the all-atom MD-derived free energy for the insertion of ethanol from the bulk aqueous phase to the hydrophobic core of the POPC-CHOL lipid bilayer, we successfully determined all the missing non-bonding interaction parameters for the POPC-CHOL-EtOH-water system. The proposed force field was applied to investigate the effect of ethanol at various concentrations on unilamellar vesicles composed of POPC and cholesterol. It was found that 40 mol% or more concentration of ethanol is required to disintegrate or rupture the POPC-CHOL vesicle membranes. While cholesterol offers some resilience against the detrimental effects of ethanol, we still observe an increase in vesicle size (swelling) and a contraction in the bilayer thickness (thinning) as ethanol concentration rises from 0 to 30 mol%. At ethanol concentrations exceeding 30 mol%, the vesicles become increasingly susceptible to disintegration due to enhanced penetration of ethanol and water molecules into the hydrophobic core of the membranes.

中文翻译：

从粗粒分子动力学中对乙醇驱动的含胆固醇仿生囊泡的溶胀和破坏的机制见解

我们进行了粗粒（CG）分子动力学（MD）模拟，以描述乙醇（EtOH）对含有仿生双层和由 1-棕榈酰-2-油酰-sn-甘油-3-磷酸胆碱（POPC）脂质组成的囊泡的胆固醇（CHOL）的影响。我们首先推导出了 SPICA/SDK CG 力场（CG-FF）中 POPC-CHOL-EtOH-water 系统缺失的相互作用参数。通过监测电子密度分布、取向有序参数，并再现乙醇从本体水相插入到 POPC-CHOL 脂质双层的疏水核心的全原子 MD 衍生的自由能，我们成功地确定了 POPC-CHOL-EtOH-水系统的所有缺失的非键合相互作用参数。所提出的力场用于研究不同浓度的乙醇对由 POPC 和胆固醇组成的单层囊泡的影响。研究发现，需要 40 mol% 或更高浓度的乙醇才能分解或破裂 POPC-CHOL 囊泡膜。虽然胆固醇对乙醇的有害影响具有一定的弹性，但当乙醇浓度从 0 mol 上升到 30 mol% 时，我们仍然观察到囊泡大小增加（肿胀）和双层厚度收缩（变薄）。当乙醇浓度超过 30 mol% 时，由于乙醇和水分子对膜疏水核心的渗透增强，囊泡变得越来越容易崩解。

更新日期：2025-03-13

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